OPIOID AND ANTIEMETIC COMBINATION COMPOSITIONS FOR INCREASED PAIN RELIEF

1 . A method for providing increased pain relief to a subject in need thereof, the method comprising:

administering to a subject that previously experienced nausea or vomiting after administration of an opioid analgesic without an antiemetic a solid oral pharmaceutical composition that comprises:

a controlled-release matrix that comprises an effective amount of the opioid analgesic to treat pain and one or more of silicified microcrystalline cellulose, hydroxypropyl methylcellulose, magnesium stearate, and stearic acid, wherein the opioid analgesic is hydrocodone or a pharmaceutically acceptable salt thereof, or oxycodone or a or a pharmaceutically acceptable salt thereof; and

an immediate-release matrix that comprises an effective amount of the antiemetic to reduce or prevent nausea associated with the opioid analgesic or vomiting associated with the opioid analgesic and one or more of silicified microcrystalline cellulose, croscarmellose sodium, and magnesium stearate, wherein the antiemetic is promethazine or a pharmaceutically acceptable salt thereof, and

wherein administration of the solid oral pharmaceutical composition provides increased pain relief to the subject compared to (i) administration of a solid oral pharmaceutical composition that comprises the opioid analgesic without the antiemetic to the subject and (ii) compared to administration of the solid oral pharmaceutical composition to a subject that did not previously experienced nausea or vomiting after administration of the opioid analgesic without the antiemetic.

2 . The method of claim 1 , wherein the controlled-release matrix further comprises an effective amount of a non-opioid analgesic to treat pain.

3 . The method of claim 2 , wherein the antiemetic has a Tmax that is less than about 6 hours from administration as measured in a non-fasting subject.

4 . The method of claim 3 , wherein the antiemetic has a Tmax that is less than about 5.5 hours from administration as measured in a non-fasting subject.

5 . The method of claim 3 wherein the antiemetic has a Tmax that is about 5.24 hours from administration as measured in a non-fasting subject.

6 . The method of claim 2 , wherein the antiemetic has an absorption AUC 0-1 of about 0.15 (h*ng/mL) as measured in a non-fasting subject an hour after administration.

7 . The method of claim 2 , wherein the increased pain relief is about 10% or more increased compared to a subject administered a solid oral pharmaceutical composition that comprises the opioid analgesic and the non-opioid analgesic without the antiemetic.

8 . The method of claim 2 , wherein the increased pain relief is for severe pain.

9 . The method of claim 8 , wherein the increased severe pain relief is about 25% or more increased over the initial 24 hours following a first administration compared to a subject administered a solid oral pharmaceutical composition that comprises the opioid analgesic and the non-opioid analgesic without the antiemetic.

10 . The method of claim 2 , wherein the increased pain relief is measured by a greater than 30% reduction in pain intensity following administration of the solid oral pharmaceutical composition.

11 . The method of claim 2 , comprising a relative reduction in the risk of vomiting of at least 50% for the 24 hours or more following administration of the solid oral pharmaceutical composition.

12 . The method of claim 2 , wherein the subject has increased pain relief during the initial 6 hours post administration.

13 . The method of claim 2 , wherein the subject experiences a reduced need for a supplemental antiemetic during the initial 6 hours or initial 24 hours post-administration.

14 . The method of claim 2 , wherein the subject experiences no need for a supplemental analgesic during the initial 6 hours or initial 24 hours post-administration.

15 . The method of claim 2 , wherein the subject is administered the solid oral pharmaceutical composition every four to six hours.

16 . The method of claim 1 , wherein the subject is a post-operative subject.

17 . The method of claim 1 , wherein the pain is moderate to severe pain.

18 . The method of claim 1 , wherein the pain is severe pain.

19 . The method of claim 1 , wherein the pain is acute pain.

20 . The method of claim 1 , wherein the solid oral pharmaceutical composition does not cause increased sedation.

21 . A method for providing increased pain relief and increase reduction or prevention of opioid induced nausea or vomiting (OINV) to a subject in need thereof, the method comprising:

administering to a subject the subject previously experienced nausea or vomiting after administration of an opioid analgesic without an antiemetic a solid oral pharmaceutical composition that comprises:

a controlled-release matrix that comprises an effective amount of the opioid analgesic to treat pain and one or more of silicified microcrystalline cellulose, hydroxypropyl methylcellulose, magnesium stearate, and stearic acid, wherein the opioid analgesic is hydrocodone or a pharmaceutically acceptable salt thereof, or oxycodone or a pharmaceutically acceptable salt thereof; and

an immediate-release matrix that comprises an effective amount of the antiemetic to reduce or prevent OINV and one or more of silicified microcrystalline cellulose, croscarmellose sodium, and magnesium stearate, wherein the antiemetic is promethazine or a pharmaceutically acceptable salt thereof, and

wherein administration of the solid oral pharmaceutical composition provides increased pain relief and increased reduction or prevention of opioid induced nausea or vomiting to the subject compared to (i) administration of a solid oral pharmaceutical composition that comprises the opioid analgesic without the antiemetic to the subject and (ii) compared to administration of the solid oral pharmaceutical composition to a subject that did not previously experienced nausea or vomiting after administration of the opioid analgesic without the antiemetic.